A novel benzodiazepine derivative that suppresses microtubule dynamics and impairs mitotic progression

Vittoria Pirani (1, 2) , Mathieu Métivier (2) , Emmanuel Gallaud (2) , Alexandre Thomas (2) , Siou Ku (2) , Denis Chrétien (2) , Roberta Ettari (3) , Régis Giet (2) , Lorenzo Corsi (1) , Christelle Benaud (2)

1 UNIMORE - Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia
2 IGDR - Institut de Génétique et Développement de Rennes
3 UniMe - Università degli Studi di Messina = University of Messina

A novel 2,3-benzodiazepine-4 derivative, named 1g, has recently been shown to function as an anti-proliferative compound. We now show that it perturbs the formation of a functional mitotic spindle, inducing a spindle assembly checkpoint (SAC)-dependent arrest in human cells. Live analysis of individual microtubules indicates that 1g promotes a rapid and reversible reduction in microtubule growth. Unlike most anti-mitotic compounds, we found that 1g does not interfere directly with tubulin or perturb microtubule assembly in vitro The observation that 1g also triggers a SAC-dependent mitotic delay associated with chromosome segregation in Drosophila neural stem cells, suggests that it targets a conserved microtubule regulation module in humans and flies. Altogether, our results indicate that 1g is a novel promising anti-mitotic drug with the unique properties of altering microtubule growth and mitotic spindle organization.

Keywords: microtubules; mitosis; anti-mitotic drug; microtubule dynamics; SAC 23

Domains: Life Sciences [q-bio]

Vittoria Pirani, Mathieu Métivier, Emmanuel Gallaud, Alexandre Thomas, Siou Ku, et al.. A novel benzodiazepine derivative that suppresses microtubule dynamics and impairs mitotic progression. Journal of Cell Science, 2020, 133 (7), pp.jcs239244. ⟨10.1242/jcs.239244⟩. ⟨hal-02543756⟩